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Can Perioperative Interventions During Cancer Surgery Affect Recurrence or Metastasis?

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Perioperative Medicine – Current Controversies

Abstract

Cancer continues to be a key cause of morbidity and mortality worldwide and its overall incidence continues to increase. Anaesthetists are increasingly faced with the challenge of managing cancer patients, either for surgical resection to debulk or excise the primary tumour, surgical emergencies in patients on chemotherapy, or for the analgesic management of acute or chronic pain. Metastatic recurrence is usually the cause of death in cancer patients. There is some experimental data suggesting that surgery, some general anaesthetics, acute postoperative pain and opioid analgesics may accelerate tumour growth and potentially increase the risk of metastatic recurrence. It has been hypothesized that awareness of perioperative factors promoting metastasis could enable designing anaesthetic and analgesic techniques that might attenuate these factors and reduce recurrence or metastasis. Evaluation of emerging literature indicates a signal from cell culture models of cancer cell growth supporting aspects of this hypothesis. Retrospective clinical studies of the association between various anaesthetic techniques, including regional anaesthesia, have yielded conflicting results. Currently, the most compelling evidence is for a direct effect of amide local anaesthetics on cancer cell metastatic potential, inhibiting migration by both a sodium channel and intracellular signaling mechanisms. Only prospective, randomized, clinical trials can prove a cause-and-effect link between anaesthetic technique and cancer. Although a number are ongoing, they are necessitate prolonged patient follow-up and large patient numbers, but their results will inform best practice in the perioperative care of cancer patients.

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References

  1. World cancer reports 2014. http://www.who.int/mediacentre/factsheets/fs297/en/

  2. Fidler IJ (2003) The pathogenesis of cancer metastasis: the “seed and soil” hypothesis revisited. Nat Rev Cancer 3:453–458

    Article  CAS  PubMed  Google Scholar 

  3. Chu GC, Chung LW (2014) RANK-mediated signaling network and cancer metastasis. Cancer Metastasis Rev 33(2–3):497–509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Santos MF, Mannam VKR, Craft BS, Puneky LV, Sheehan NT, Lewis RE, Cruse JM (2014) Comparative analysis of innate immune system function in metastatic breast, Colorectal, and prostate cancer patients with circulating tumour cells. Exp Mol Pathol 96(3):367–374

    Article  CAS  PubMed  Google Scholar 

  5. Melamed R, Bar-Yosef S, Shakhar G, Shakhar K, Ben-Eliyahu S (2003) Suppression of natural killer cell activity and promotion of tumour metastasis by ketamine, thiopental, and halothane, but not by propofol: mediating mechanisms and prophylactic measures. Anesth Analg 97(5):1331–1339

    Article  CAS  PubMed  Google Scholar 

  6. Buckley A, McQuaid S, Johnson P, Buggy DJ (2014) Effect of anaesthetic technique on the natural killer cell anti-tumour activity of serum from women undergoing breast cancer surgery: a pilot study. Br J Anaesth 113(suppl 1):i56–i62. Oxford University Press

    Article  CAS  PubMed  Google Scholar 

  7. Pages F, Galon J, Dieu-Nosjen M-C, Tartour E, Sautes-Fridman C, Fridman W-H (2010) Immune infiltration in human tumors: a prognostic factor that should not be ignored. Oncogene 29:1093–1102

    Article  CAS  PubMed  Google Scholar 

  8. Qian B, Deng Y, Im JH, Muschel RJ, Zou Y, Lang RA, Pollard JW (2009) A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth. PLoS One 4(8):e6562

    Article  PubMed  PubMed Central  Google Scholar 

  9. Ostrand-Rosenberg S, Sinha P (2009) Myeloid-derived suppressor cells: linking inflammation and cancer. J Immunol 182(8):4499–4506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Loop T, Dovi-Akue D, Frick M, Roesslein M, Egger L, Humar M, Hoetzel A, Schmidt R, Borner C, Pahl HL, Geiger KK, Pannen BH (2005) Volatile anesthetics induce caspase-dependent, mitochondria-mediated apoptosis in human T-lymphocytes in vitro. Anesthesiology 102(6):1147–1157

    Article  CAS  PubMed  Google Scholar 

  11. Neeman E, Ben-Eliyahu S (2013) Surgery and stress promote cancer metastasis: new outlooks on perioperative mediating mechanisms and immune involvement. Brain Behav Immun 30 Suppl:S32–S40

    Article  PubMed  Google Scholar 

  12. Buggy DJ, Smith G (1999) Epidural anaesthesia and analgesia, better outcome after major surgery? Growing evidence suggests so. BMJ 319(7209):530–531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Goldfarb Y, Ben-Eliyahu S (2006) Surgery as a risk factor for breast cancer recurrence and metastasis: mediating mechanisms and clinical prophylactic approaches. Breast Dis 26:99–114

    PubMed  Google Scholar 

  14. Carmeliet P (2005) Angiogenesis in life, disease and medicine. Nature 438(70707):932–936

    Article  CAS  PubMed  Google Scholar 

  15. Exadaktylos AK, Buggy DJ, Moriarty DC, Mascha E, Sessler DI (2006) Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis? Anesthesiology 105(4):660–664

    Article  PubMed  PubMed Central  Google Scholar 

  16. Ecimovic P, Murray D, Doran P, Buggy DJ (2014) Propofol and bupivacaine in breast cancer cell function in vitro – role of the NET1 gene. Anticancer Res 34(3):1321–1331

    CAS  PubMed  Google Scholar 

  17. Huang H, Benzonana LL, Zhao H, Watts HR, Perry NJS, Bevan C, Brown R, Ma D (2014) Prostate cancer cell malignancy via modulation of HIF-1α pathway with isoflurane and propofol alone and in combination. Br J Cancer 111:1338–1349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Jaura AI, Flood G, Gallagher HC, Buggy DJ (2014) Differential effects of serum from patients administered distinct anaesthetic techniques on apoptosis in breast cancer cells in vitro: a pilot study. Br J Anaesth 113(Suppl1):i63–i67. I. Oxford University Press

    Article  CAS  PubMed  Google Scholar 

  19. Looney M, Doran P, Buggy DJ (2010) Effect of anesthetic technique on serum vascular endothelial growth factor C and transforming growth factor β in women undergoing anesthesia and surgery for breast cancer. Anesthesiology 113(5):1118–1125

    Article  CAS  PubMed  Google Scholar 

  20. Ohta N, Ohashi Y, Fujino Y (2009) Ketamine inhibits maturation of bone marrow-derived dendritic cells and priming of the Th1-type immune response. Anesth Analg 109:793–800

    Article  CAS  PubMed  Google Scholar 

  21. Ecimovic P, McHugh B, Murray D, Doran P, Buggy DJ (2013) Effects of sevoflurane on breast cancer cell function in vitro. Anticancer Res 33(10):4255–4260

    CAS  PubMed  Google Scholar 

  22. Kawaraguchi Y, Horikawa YT, Murphy AN (2011) Volatile anesthetics protect cancer cells against tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis via caveolins. Anesthesiology 115(3):499–508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Benzonana LL, Perry N, Watt HR, Yang B, Perry IA, Coombes C, Takata M, Ma D (2013) Isoflurane, a commonly used volatile anesthetic enhances renal cancer growth and malignant potential via the hypoxia-inducible factor cellular signaling pathway in vitro. Anesthesiolog 119:593–605

    Article  CAS  Google Scholar 

  24. Shi QY, Zhang SJ, Liu L, Chen QS, Yu LN, Zhang FJ, Yan M (2015) Sevoflurane promotes the expansion of glioma stem cells through activation of hypoxia-inducible factors in vitro. Br J Anaesth 114(5):715–716

    Article  Google Scholar 

  25. Luo X, Zhao H, Hennah L, Ning J, Liu J, Tu H, Ma D (2015) Impact of isoflurane on malignant capability of ovarian cancer in vitro. Br J Anaesth 114(5):831–839

    Article  CAS  PubMed  Google Scholar 

  26. Ash SA, Valchev GI, Looney M, Ni Mhathuna A, Crowley PD, Gallagher HC, Buggy DJ (2014) Xenon decreases cell migration and secretion of a pro-angiogenesis factor in breast adenocarcinoma cells: comparison with Sevoflurane. Br J Anaesth 113(suppl 1):i14–i21

    Article  CAS  PubMed  Google Scholar 

  27. Myles PS, Leslie K, Chan MTV, Forbes A, Peyton PJ, Paech MJ, Beattie WS, Sessler DI, Devereaux PJ, Silbert B, Schricker T, Wallace S (2014) The safety of addition of nitrous oxide to general anaesthesia in at-risk patients having major non-cardiac surgery (ENIGMA-II): a randomised, single-blind trial. Lancet 384(9952):1446–1454

    Article  CAS  PubMed  Google Scholar 

  28. Fleischmann E, Marschalek C, Schlemitz K (2009) Nitrous oxide may not increase the risk of cancer recurrence after colorectal surgery: a follow-up of a randomized controlled trial. BMC Anesthesiol 9:1

    Article  PubMed  PubMed Central  Google Scholar 

  29. Forget P, Collet V, Lavand’homme P, De Kock M (2010) Does analgesia and condition influence immunity after surgery? Effects of fentanyl, ketamine and clonidine on natural killer activity at different ages. Eur J Anaesthesiol 27(3):233–240

    Article  PubMed  Google Scholar 

  30. Franchi S, Moretti S, Castelli M et al (2012) Mu opioid receptor activation modulates toll like receptor 4 in murine macrophages. Behav Immun 26(3):480–488

    Article  CAS  Google Scholar 

  31. Maher DP, Wong W, White PF, McKenna R, Roster H, Shamloo B, Louy C, Wender R, Yumul R, Zhang V (2014) Association of increased postoperative opioid administration with non-small-cell lung cancer recurrence: a retrospective analysis. Br J Anaesth 113(suppl 1):i4–i13

    Article  Google Scholar 

  32. Singleton PA, Mirzapoiazova T, Hasina R, Salgia R, Moss J (2014) Increased μ-opioid receptor expression in metastatic lung cancer. Br J Anaesth 113(suppl 1):i4–i1356

    Article  Google Scholar 

  33. Lin X, Wang YJ, Li Q, Hou YY, Hong MH, Cao YL, Chi ZO, Liu JG (2009) Chronic high-dose morphine treatment promotes SH-SY5Y cell apoptosis via c-Jun N-terminal kinase-mediated activation of mitochondria-dependent pathway. FEBS J 276(7):2022–2036

    Article  CAS  PubMed  Google Scholar 

  34. Sarkar DK, Zhang C, Murugan S, Dokur M, Boyadjieva NI, Ortiguela M, Reuhl KR, Mojtehedzadeh S (2011) Transplantation of β endorphin neurons into the hypothalamus promotes immune function and restricts the growth and metastasis of mammary carcinoma. Cancer Res 71(19):6282–6291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Sarkar DK, Murugan S, Zhang C, Boyadjieva N (2012) Regulation of cancer progression by β endorphin neuron. Cancer Res 72(4):836–840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Soslow RA, Dannenberg AJ, Rush D, Woerner BM, Khan KM, Masferrer J, Koki AT (2000) COX-2 is expressed in human pulmonary, colonic, and mammary tumors. Cancer 89(12):2637–2645

    Article  CAS  PubMed  Google Scholar 

  37. Cheng I, Liu X, Plummer SJ, Krumroy LM, Casey G, Whitte JS (2007) COX2 genetic variation, NSAIDs, and advanced prostate cancer risk. Br J Cancer 97:557–561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Brown JR, DuBois RN (2005) COX-2: a molecular target for colorectal cancer prevention. J Clin Oncol 23(12):2840–2855

    Article  CAS  PubMed  Google Scholar 

  39. Singh B, Berry JA, Shoher A, Ramakrishnan V, Lucci A (2005) COX-2 overexpression increases motility and invasion of breast cancer cells. Int J Oncol 26(5):1393–1399

    CAS  PubMed  Google Scholar 

  40. Rothwell PM, Fowkes F, Belch J, Ogawa H, Warlow CP, Meade TW (2011) Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet 377(9759):31–41

    Article  CAS  PubMed  Google Scholar 

  41. Harris RE, Beebe-Donk J, Doss H, Doss DB (2005) Aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs in cancer prevention: a critical review of non-selective COX-2 blockade. Oncol Rep 13(4):559–583 (25)

    CAS  PubMed  Google Scholar 

  42. Forget P, Bentin C, Machiels J-P, Berliere M, Coulie PG, De Kock M (2014) Intraoperative use of ketorolac or diclofenac is associated with improved disease-free survival and overall survival in conservative breast cancer surgery. Br J Anaesth 113(suppl 1):i82–i87

    Article  CAS  PubMed  Google Scholar 

  43. Singh PP, Lemanu DP, Taylor M, Hill AG (2014) Association between preoperative glucocorticoids and long-term survival and cancer recurrence after colectomy: follow-up analysis of a previous randomized controlled trial. Br J Anaesth 113(suppl 1):i4–i13

    Article  Google Scholar 

  44. Fraser SP, Foo I, Djamgoz M (2014) Anaesthetic use in cancer surgery and disease recurrence: role of voltage-gated sodium channels. Br J Anaesth 113(6):899–902

    Article  CAS  PubMed  Google Scholar 

  45. Baptista-Hon DT, Robertson FM, Robertson GB, Owen SJ, Rogers GW, Lydon EL, Lee NH, Hales TG (2014) Potent inhibition by ropivacaine of metastatic colon cancer SW620 cell invasion and NaV1.5 channel function. Br J Anaesth 113(suppl 1):i39–i48

    Article  CAS  PubMed  Google Scholar 

  46. Lirk P, Berger R, Hollmann MW et al (2012) Lidocaine time- and dose-dependently demethylates deoxyribonucleic acid in breast cancer cell lines in vitro. Br J Anaesth 109(2):200–207

    Article  CAS  PubMed  Google Scholar 

  47. Piegeler T, Votta-Velis EG, Liu G, Place AT, Schwartz DE, Beck-Schimmer B, Minshall RD, Borgeat A (2012) Antimetastatic potential of amide-linked local anesthetics: inhibition of lung adenocarcinoma cell migration and inflammatory Src signaling independent of sodium channel blockade. Anesthesiology 117(3):548–559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Li K, Yang J, Han X (2014) Lidocaine sensitizes the cytotoxicity of cisplatin in breast cancer cells via up-regulation of RARβ2 and RASSF1A demethylation. Int J Mol Sci 15(12):23519–23536

    Article  PubMed  PubMed Central  Google Scholar 

  49. Lirk P, Hollmann MW, Fleischer M, Weber NC, Fiegl H (2014) Lidocaine and ropivacaine, but not bupivacaine, demethylate deoxyribonucleic acid in breast cancer cells in vitro. Br J Anaesth 113(suppl 1):i32–i38

    Article  CAS  PubMed  Google Scholar 

  50. Ash SA, Buggy DJ (2013) Does regional anaesthesia and analgesia or opioid analgesia influence recurrence after primary cancer surgery? An update of available evidence. Best Pract Res Clin Anaesthesiol 27(4):441–456

    Article  PubMed  Google Scholar 

  51. Biki B, Mascha E, Moriarty DC, Fitzpatrick JM, Sessler DI, Buggy DJ (2008) Anesthetic technique for radical prostatectomy surgery affects cancer recurrence: a retrospective analysis. Anesthesiology 109:180–187

    Article  PubMed  Google Scholar 

  52. Wuethrich PY, Thalmann GN, Studer UE, Burkhard FC (2013) Epidural analgesia during open radical prostatectomy does not improve long-term cancer-related outcome: a retrospective study in patients with advanced prostate cancer. PLoS One 8(8):e72873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Merquiol F, Montelimard A-S, Nourissat A, Molliex S, Zufferey PJ (2013) Cervical epidural anesthesia is associated with increased cancer-free survival in laryngeal and hypopharyngeal cancer surgery: a retrospective propensity-matched analysis. Reg Anesth Pain Med 38(5):398–402

    Article  CAS  PubMed  Google Scholar 

  54. Lai R, Peng Z, Chen D, Wang X, Xing W, Zeng W, Chen M (2012) The effects of anesthetic technique on cancer recurrence in percutaneous radiofrequency ablation of small hepatocellular carcinoma. Anesth Analg 114(2):290–296

    Article  PubMed  Google Scholar 

  55. de Oliveira GS Jr, Ahmad S, Schink JC, Singh DK, Fitzgerald PC, McCarthy RJ (2011) Intraoperative neuraxial anesthesia but not postoperative neuraxial analgesia is associated with increased relapse-free survival in ovarian cancer patients after primary cytoreductive surgery. Reg Anesth Pain Med 36(3):271–277

    Article  PubMed  Google Scholar 

  56. Cummings KC 3rd, Xu F, Cummings LC, Cooper GS (2012) A comparison of epidural analgesia and traditional pain management effects on survival and cancer recurrence after colectomy, a population-based study. Anesthesiology 116(4):797–806

    Article  CAS  PubMed  Google Scholar 

  57. Conrick-Martin I, Kell MR, Buggy DJ (2012) Meta-analysis of the effect of central neuraxial regional anesthesia compared with general anesthesia on postoperative natural killer T lymphocyte function. J Clin Anesth 24(1):3–7

    Article  PubMed  Google Scholar 

  58. O’Riain SC, Buggy DJ, Kerin MJ, Watson RW, Moriarty DC (2005) Inhibition of the stress response to breast cancer surgery by regional anesthesia and analgesia does not affect vascular endothelial growth factor and prostaglandin E2. Anesth Analg 100(1):244–249

    Article  PubMed  Google Scholar 

  59. Togioka B, Galvagno S, Sumida S, Murphy J, Ouanes JP, Wu C (2012) The role of perioperative high inspired oxygen therapy in reducing surgical site infection: a meta-analysis. Anesth Analg 114(2):334–342

    Article  CAS  PubMed  Google Scholar 

  60. Cooke MS, Evans MD, Dizdaroglu M, Lunec J (2003) Oxidative DNA damage: mechanisms, mutation, and disease. FASEB J 17(10):1195–1214

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Donal J. Buggy MD, MSc, DME, FRCPI, FCAI, FRCA .

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Abdelrahman, D., Buggy, D.J. (2016). Can Perioperative Interventions During Cancer Surgery Affect Recurrence or Metastasis?. In: Stuart-Smith, K. (eds) Perioperative Medicine – Current Controversies. Springer, Cham. https://doi.org/10.1007/978-3-319-28821-5_14

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  • DOI: https://doi.org/10.1007/978-3-319-28821-5_14

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